National Optimal Lung Cancer Pathway (NOLCP) Update 2024: Referral to Treatment Version 4.0

1. National Optimal Lung Cancer Pathway (NOLCP) For suspected and confirmed lung cancer: Referral to treatment UPDATE 2024 Version 4.0 Introduction This optimal pathway is primarily designed to improve outcomes in lung cancer by encouraging best practice, reducing variation,and reducing delays in diagnosis,stagingand treatment. Use of guidelines The diagnosis, staging and fitness assessments in this pathway should be completed with reference to current national guidelines. The NOLCP is also supported by a series of Diagnostic Standards of Care that provide more detail (see Appendix 1), and the Commissioning Guidance for effective lung cancer services. Maximum waiting times (calendar days unless otherwise specified) The times in each step of the pathway, shown on the left, are the maximum recommended; the majority of steps should be completed before the specified maximum. The maximum recommended time to commencement of treatment is 49 calendar days, even though the national cancer wait times target is unchanged at 62 calendar days. A randomised controlled trial showed a reduction of time to diagnosis from 29 to 15 days was associated with a longer median survival of 503 days compared with 312. The start point of the cancer waiting time pathway is the date of referral on the cancer pathway, or date of upgrade to the cancer pathway once the diagnosisof cancer is suspected;this can be based on chestX-ray or CT. Key time points for monitoring are: time to CT; time to diagnostic clinic; time to full diagnosis and staging; and time to first treatment. A note for commissioners The initial identification and referral of patients with suspected lung cancer is often dependent on primary care. Prompt recognition, risk assessment and referral is essential to reduce delay in diagnosis and to reduce the high proportion of lung cancer patients who are diagnosed via emergency admissions. Most of the diagnosis, staging and treatment of lung cancer is provided by secondary and tertiary care; primary care may be involved in supportive care throughout. Supportive, palliative and end of life care is provided by both primary and secondary care. Please refer to the updated Commissioning Guidance that sets out the requirements of the service to ensure the NOLCP is delivered. Key features: • Potential to reduce delay from CXR to CT and triage to less than 24 hours • Direct to CT for high-risk patients • Potential avoidance of emergency admission • Allows triaged patients to be managed by primary or secondary care • Timed treatment pathways supporting rapid progress to treatment Requirements: • Turnaround times have to be short, across the whole pathway; . • Hot reporting of all CXRs and subsequent CTs • Daily respiratory medicine cancer clinic optimal • Well organised scheduling of appointments for therapies • Team based approach to radiation planning and dedicated peer review / planning meeting • Local access to advanced radiotherapy planning and treatment What is new in the update? • Inclusion of direct to CT (without CXR) for patients at high-risk of symptomatic lung cancer • Clarification of other urgent route presentation • Inclusion of blood-based tumour diagnostics e.g. circulating tumour DNA (ctDNA) • Inclusion of molecular testing pathway

2. National Optimal Lung Cancer Pathway For suspected and confirmed lung cancer: Referral to treatment UPDATE 2024 Version 4.0 GP Other referral route E.g. post discharge, incidental finding on imaging (screen detected my go direct to clinic) Inpatient referrals for suspected lung cancer Maximum times (calendar days) Yes High Risk of Lung Cancer? Direct referral route No No Throughout pathway: • consider entry into a research trial • offer supportive & palliative care, e.g. by LCNS, GP, specialists in palliative care • encourage smoking cessation CT within 24h if clinically indicated; inpatients seen within 48h by acute oncology, respiratory and/or supportive/palliative services Urgent or routine CXR CXRsuspicious of lung cancer? (reported before patient leaves department or within 24h.) CT not indicated Day -3-0 CT suspicious of lung cancer? Yes No CT same day / within 72h Yes Manage Day 0-3 TRIAGE (*1,2) - by radiology or respiratory medicine according to local protocol - Lung cancer suspected? Yes No Direct biopsy option; (*3) Lung cancer unlikely (*1 &2) Further management according to local protocol with options of further management of CT findings by primary care or secondary care Fast track lung cancer clinic. Assessment by LCNS. Diagnostic process plan / diagnostic planning meeting prior to clinic. Treatment of co-morbidity and palliation / treatment of symptoms / prehabilitation and smoking cessation. Consider predictive blood biomarker. Day 1-6 Suitable for potentially curative treatment? # Yes No Curative Intent Management pathway (*4) Test bundle requested at first OPA incl. at least: PET-CT, spirometry, brain imaging and as required: detailed lung function and cardiac assessment / ECHO. LCNS clarify/reassure re complex pathway. Will pathological diagnosis influence treatment and is potential treatment appropriate to patient’s wishes? No Yes Investigations to yield maximum diagnostic AND staging information with least harm. Results available within 3 working days for subtype and 10 working days / 14 calendar days for molecular markers (see genomic and molecular pathway *5). Clinical diagnosis or patient preference means no biopsy required. Yes Further investigation(s) indicated? No Day 21 (Day 18 SCLC) Full MDT discussion of treatment options Yes Yes No cancer: Manage/discharge Further discussion needed? Further investigation(s)? No No Day 28 Follow-up Lung Cancer Clinic Cancer Confirmed and treatment options discussed. Research trial considered. LCNS Support in practical aspects *Refer to separate numbered pathway detail # Low threshold for curative intent pathway; may discuss with wider MDT if unsure OPA with treating specialist within 3 working days of completed investigations (full molecular analysis, staging and fitness) Day 33 Some or all diagnosis and staging tests may be in a tertiary centre Yes Further investigation(s)? Day 42 + all patients with stage IV cancer should be routinely offered an assessment No Day 49£ First Treatment £ Reflects the aim for reduced time to treatment; the national target remains 62 days Other palliative treatments Systemic treatment Radiotherapy Specialist supportive/ palliative care + Surgery Maximum times

3. Pathway Detail 1 Triage system for referrals to the lung cancer service: secondary care leads the management process Triage refers to the process of selecting the appropriate route based on clinical data. This pathway places the responsibility for managing all patients referred for suspected lung cancer within secondary care. It ensures patients with other conditions that may require secondary care are given appointments and patients not requiring secondary care are directed back to primary care. TRIAGE Respiratory physician ±radiologist triages with CT and clinical features Lung cancer likely? Yes No Non lung cancer pathway Fast track lung cancer clinic. Diagnostic process plan / diagnostic planning meeting prior to clinic. Treatment of co-morbidity and palliation / treatment of symptoms. LCNS: Prehabilitation/social/psychological assessment. Clarity/reassurance re complex tests and next steps Respiratory condition requiring urgent appointment including other cancer? Yes No Lung cancer pathway Urgent respiratory clinic or other fast track cancer referral Urgent non- respiratory condition? Yes No Urgent communication with GP or direct admission depending on condition found or suspected Ongoing symptoms / need for non-urgent respiratory OPA? Write to GP and patient Yes No Non-urgent respiratory OPA Including management of pulmonary nodules GP meets/communicates with patient. Still requires respiratory OPA? Yes No GP manages patient Recommendations for the management of pulmonary nodules can be found in the British Thoracic Society guidelines on the investigation and management of pulmonary nodules.

4. Pathway Detail 2 Triage system for referrals to the lung cancer service: primary care leads the management process Triage refers to the process of selecting the appropriate route based on clinical data. This pathway places the responsibility for managing all patients referred for suspected lung cancer within secondary care. It ensures patients with other conditions that may require secondary care are given appointments and patients not requiring secondary care are directed back to primary care. TRIAGE Radiologist (±respiratory physician input triages according to CT and clinical features Lung Cancer Likely? Yes No Fast track lung cancer clinic. Diagnostic process plan / diagnostic planning meeting prior to clinic. Treatment of co-morbidity and palliation / treatment of symptoms. LCNS: Prehabilitation/social/psychological assessment. Clarity/reassurance re complex tests and next steps Non lung cancer pathway Condition requiring urgent appointment including other cancer? Yes No Lung cancer pathway Refer for urgent clinic / admission or other fast track cancer referral Non-urgent condition? Yes No Manage in primary care or non-urgent referral Management of pulmonary is included here GP manages patient Recommendations for the management of pulmonary nodules can be found in the British Thoracic Society guidelines on the investigation and management of pulmonary nodules.

5. Pathway Detail 3 Direct to biopsy variation This pathway allows for early diagnostic biopsy where other tests are not required for staging and treatment. Such patients include those that have obvious advanced disease that is not suitable for treatment with curative intent. Patients potentially suitable for curative intent generally require a PET-CT to clarify diagnosis (for small pulmonary nodules) staging and the most appropriate first diagnostic and staging investigation. Direct biopsy investigations include neck ultrasound guided biopsy, percutaneous lung biopsy, endobronchial ultrasound needle biopsy, pleural aspiration and pleural biopsy. The direct biopsy pathway has the potential to provide a rapid diagnosis for some patients where detailed staging and fitness investigations are not needed to guide management. Direct biopsy can also include blood predictive biomarker testing (“liquid biopsy”). TRIAGE By radiology or respiratory medicine according to local protocol Lung Cancer Likely? No Manage Yes Suitable for potentially curative treatment? No Yes Will pathological diagnosis influence treatment and is potential treatment appropriate to patient’s wishes? Yes No Clinical diagnosis or patient preference means no biopsy required. No No Staging investigation not required to guide management Yes Direct to biopsy; same day or within calendar 3 days Yes Fast track lung cancer clinic. Diagnostic process plan / diagnostic planning meeting prior to clinic Treatment of co-morbidity and palliation / treatment of symptoms LCNS: Prehabilitation/social/psychological assessment. Clarity/reassurance re complex tests and next steps Consider predictive blood biomarker National Optimal Pathway

6. Pathway detail 4 National Optimum Curative Intent Management Pathway Patients who are potentially suitable for curative treatment usually require multiple investigations to accurately assess their diagnosis, stage and fitness. The capacity to provide rapid access to these investigations may be limited and so the logistics of scheduling needs to be optimised to prevent long waiting times. This pathway fast tracks these patients by requesting tests concurrently, supported by pre-planned availability of urgent test appointments e.g. lung biopsy, bronchoscopy, endobronchial ultrasound, mediastinoscopy, ECHO and complex lung function. Reference should be made to the NICE guidelines for the investigation and management of suspected lung cancer. To prevent delays in treatment, consider early notification of thoracic surgeons or clinical oncology to help with scheduling. Fast track lung cancer clinic ±diagnostic planning meeting / Diagnostic MDT Assessment by lung cancer nurse specialist* Stage: Potentially T1-3 N0-2 M0 (N2 non-bulky; i.e. <3cm) Or locally advanced; potential for radical RT? May include selected patients with oligometastatic disease No Yes Potentially fit enough for treatment with curative intent and willing to consider this? (Ensure low threshold for proceeding with work up for curative treatment) No Yes Simultaneous fast track: Patients with borderline fitness$add: • Preoperative rehabilitation • Shuttle walk test / CPEX / ECHO • Perfusion scan if required • Early cardiology assessment for cardiac co-morbidity All patients: • Medical optimisation (incl. smoking cessation) • PET-CT (within 5 calendar days) • Diagnostic and staging tests, inc. brain imaging • Spirometry ±TLCO • Complete all tests within 14 calendar days • Alert surgeons / clinical oncology Usual diagnosis and staging pathway Full MDT Discussion of treatment options or further investigation Yes Yes Further discussion needed? Further investigation(s)? No No Follow-up Lung Cancer Clinic Cancer confirmed and treatment options discussed. Research trial considered. LCNS Support* LCNS Support* Prehabilitation/social/psychological assessment. Clarity/reassurance re complex tests and next steps OPA with treating specialist (within 3 working days) Yes Further investigation(s)? No First Treatment $There is no agreed definition of borderline fitness. Here this is taken as a level of fitness that could lead to a greater than average morbidity or mortality from surgery. However, modern radiotherapy techniques mean that most patients this category can be treated with potentially curative intent.

7. Pathway detail 5 National Optimum Genomic and Molecular Pathway Systemic anticancer treatment (SACT) for lung cancer is increasingly complex but has the potential to transform outcomes if it is given promptly when patients are still fit enough to benefit. Some patients deteriorate whilst waiting for tests to be completed and delays to full molecular analysis (including genomics and other markers necessary to choose optimum SACT) must be avoided. The time from acquisition of sample to full molecular report available to clinicians should be no more than 14 calendar days. NOLCP Maximum Times Molecular pathway times Fast track lung cancer clinic. Assessment by LCNS. Consider predictive blood biomarker† Day 1-6 Will pathological diagnosis influence treatment and is potential treatment appropriate to patient’s wishes? Yes Tissue acquired; consider additional samples for molecular testing Day 0 Morphological examination including slide preparation for reflex testing Day 1-3 Insufficient tissue Sufficient tissue Small cell or other primary Non-small cell Pathology email / phone lung MDT same day Yes Suitable for repeat sampling? Discuss before next MDT PD-L1 testing and slide prep for NGS by local pathology No Reflex NGS Testing* Insufficient tissue DNA salvage / limited panel FISH (ALK / ROS1) Blood predictive biomarker Day 21 Day 14 Full MDT discussion of treatment options (Can occur before full molecular testing result available but treating specialist should see patient within 3 working days of the result being available (14 + 3 days from sample acquisition) Day 28 Day 21 for repeat sampling *Method and composition of NGS panel may vary due to advances in therapy. Both DNA and RNA NGS should be performed in any histological subtype of NSCLC including, squamous, adenocarcinoma, mixed adenosquamous, neuroendocrine tumours with adenocarcinoma features, NSCLC NOS, and large cell. ‡Local immunohistochemistry for ALK and ROS may be performed; fast tract limited gene panel to avoid delay in neoadjuvant treatment Surgical patients: If genomic/PDL1 testing not available on diagnostic biopsy, testing should be requested on surgical specimen by parent MDT †Blood predictive biomarker testing for stage IIIB/IV and eligible performance status

8. Timed Treatment Pathway 1: Thoracic Surgery This pathway was developed by members of the CEG for Lung Cancer and Mesothelioma, NHSE and the Thoracic Surgery section of the Society of Cardiothoracic Surgeons. It was led by D West and S Barnard. Maximum Times Best Practice Pointers National Optimal Lung Cancer Pathway Diagnostic Standards of Care • Electronic or structured referral document Multidisciplinary Team meeting Staging and routine fitness testing must be available A surgeon should be present for >95% of meetings Day 21 • Pooled waiting lists • Optimise comorbidities e.g. COPD, smoking, nutrition as early in the pathway as possible2. Surgical Referral (may be after neoadjuvant therapy) Surgical clinic within 3 working days Face to face optimal • Surgical clinic same day as MDT Advanced tests requested if indicated Identify potential research eligibility Surgical assessment • Protocol-based pre- operative assessment clinic Day 33 Preoperative Assessment Surgical Clinic Meet surgeon and nurse specialist Risk stratification, research trial entry • LCNS to support adjuvant chemotherapy discussion. Discuss/Refer to local prehab/ rehab services Complex Routine • Joint surgery/oncology clinics for high risk or multimodality patients If surgery too high risk or declined: direct referral on day of decision to clinical oncology or other service • Single-visit whenever possible. further testing, specialist referral, prehabilitation4, second opinion/ high risk meeting • Written information to patient • Day 48 Trial screening Direct to surgery In-Patient • Routine day of surgery admission3 • 7 day consultant ward3 rounds • Enhanced recovery perioperative care Surgery Day 58 (1) https://www.england.nhs.uk/wp-content/uploads/2017/07/thoracic-surgery-service-specification.pdf (2) NICE Lung Cancer Guideline CG122 updated 2019 https://www.nice.org.uk/guidance/ng122 (3) Cardiothoracic Surgery GIRFT Programme National Specialty Report 2018David Richens https://gettingitrightfirsttime.co.uk/wp-content/uploads/2018/04/GIRFT-Cardiothoracic-Report-1.pdf (4) Preoperative exercise training for patients with non-small cell lung cancer Cavalheri V, Granger C Cochrane Database Syst Rev 2017 Jun 7;6: CD012020 Thoracic Surgery Service Specification 170016/S . NHS England Definition of routine and advanced fitness testing Routine fitness testing includes spirometry, transfer factor, and transthoracic echocardiography, and six-minute walk testing when indicated. Tests beyond these, for example cardiopulmonary exercise testing, split function tests or cardiology investigations including perfusion scanning or angiography are defined as “advanced” for the purpose of the pathway

9. Timed Treatment Pathway 2: Systemic Therapies This pathway was developed by members of the CEG for Lung Cancer and Mesothelioma, NHSE and led by D Talbot, Y Summers, M Hatton, L Toy and S Popat. Maximum Times Best Practice Pointers National Optimal Lung Cancer Pathway Diagnostic Standards of Care • Continuous tracking and navigation • Electronic or structured referral document Multidisciplinary Team meeting Staging, Performance status, pathology including typing and molecular markers available • Day 21 (day 18 for SCLC) Fast oncology cancer within 24hours track referral for to all lung Small cell lung cancer Non-small cell lung cancer Fast track referral to: • Oncology within 24 hours • Chemotherapy suite • Pre-book chemotherapy suite • LCNS - Support patient to make informed choices and give clarity to treatments. Benefits/compensation/ community referrals Oncology Clinic (within 3 working days and latest day 25 of pathway) Face to face optimal Oncology Clinic (within 3 working days and latest day 33 of pathway) Face to face optimal information/ complex • Optimise e.g. nutrition as early in the pathway as possible2. comorbidities COPD, Day 35 (day 32 for SCLC) smoking, First Treatment (within 7 days) • Oncology clinic same day as MDT for small cell lung cancer Day 42 First Treatment (within 14 days) Adjuvant treatment: Ideally within eight weeks but no later than 16 weeks • Joint oncology chemo-radiotherapy patients clinical/medical clinics for • Single-visit possible. whenever Day 49 • Written consent in clinic • Trial screening

10. Notes: Timed Treatment Pathway 2: Systemic Therapies Goals The purpose of this document is to provide, from current best practice in the UK, suggestions on how the delivery of systemic anti-cancer therapy (SACT) for people with lung cancer might be coordinated within provider centres to achieve the objective of the NOLCP) and compliance with NICE Guidance (Currently NG122, June 2019). The goal is to enable safe, timely systemic treatment for patients with lung cancer that is coordinated efficiently by MDTs and communicated effectively with the patient, their carers’ and community. With quality assured treatment and audit, demonstrable delivery of the Long-Term Plan of the NHSwill ensure “every patient has access to optimal, personalised treatment and care and effective follow-up”. Scope This document relates to the planning and provision of SACT for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) given with curative or palliative intent by MDTs in England. This guidance is summarised in the companion Flow Chart “Timed Treatment Pathway 2: SystemicTherapy”. SACT with Curative Intent SACT is effective in improving outcomes when given as neoadjuvant and adjuvant therapy. Current evidence supports the use of neoadjuvant treatment over adjuvant, (although this may change) potential delays in treatment whilst awaiting biopsy should be discussed with the patient to arrive at a shared decision about choice of treatment. • Combined modality therapy with concurrent chemo-radiotherapy with surgery, ideally within a six-week window, is indicated for patients with operable StageIIIAN2 NSCLCwith suitable lung function and performance status. • The details of SACT and the indications are changing as evidence is published. NICE regularly update treatment algorithms as Technology Assessments are published. See: www.nice.org.uk/guidance/ng122/resources • For locally advanced unresectable NSCLC, concurrent chemo-radiotherapy followed by durvalumab maintenance therapy is the current standard of care for suitable patients (TA578). Sequential chemo-radiotherapy can be considered for those for whom concurrent therapy is contra-indicated. For stage I-III (limited) SCLC, concurrent chemo-radiotherapy is the standard of care. Sequential chemo-radiotherapy may be considered for those for whom the latter is contra-indicated. Surgical resection for early stage SCLC is possible and in such cases adjuvant combination chemotherapy with platinum and etoposide should be considered. As treatment with curative intent is invariably multi-modality in nature, it is important that care is coordinated and planned early by the MDT with information provided to patients at the appropriate time. • Systemic Therapy with Palliative Intent • People with stage IIIB or IV NSCLC having eligible PS should be offered SACT (first-line, maintenance, second-line treatments and therapies available through the CDF) in accordance with NG122. Treatment should be tailored to the pathological sub- type of the tumour, relevant somatic mutations, individual predictive factors and co-morbidities. • People with Stage IIIB/IV (Extensive Stage) SCLC should have treatment (typically combination chemotherapy with with immunotherapy) initiated within two weeks of the histological/cytological diagnosis. Co-ordinationof thePathway Following early diagnosis, staging and assessment of lung cancer, it is the responsibility of MDTs to have in place a robust, integrated pathway designed to deliver appropriate and prompt systemic therapy. It is essential, early in the pathway, to have sufficient diagnostic material for the identification of the cell type, somatic mutations, chromosome re-arrangements and immunological markers. This is a component of the “diagnostic and staging bundle” which, together with radiology and clinical information, enables the team to recommend the most appropriate therapy at the earliest opportunity. Pathway detail 5 provides guidance on meeting the 14working day turnaround from sample acquisition to full molecular result. • Patients for whom systemic therapy is recommended as first line therapy should be seen by the oncologist within three working days of the full molecular analysis becoming available. Appropriate investigations (haematological indices, liver function, renal function, molecular markers, completion of imaging) should all have been completed. The lung cancer specialist nurse (LCNS) has a key role in communication, coordination and as a point of contact throughout the patient journey. Whilst respecting patients’ need for adequate time to consider treatment and giving informed consent, it is desirable for the patient to meet the LCNS, or cancer pharmacist, before treatment commences and advanced booking of treatment in the chemotherapy suite. • Treatment of SCLC should be initiated within two weeks of the diagnosis. A “small cell lung cancer alert” should be initiated by pulmonary pathologists on suspicion of a diagnosis of SCLC. Email notification of the MDT, and others, by the thoracic pathologist within 24hrs of the diagnosis enables prompt communication with the patient, completion of investigations, advanced booking of appointments and chemotherapy scheduling before the target date. Follow upand Continuityof Care Timely review and assessment of patients undergoing systemic therapy is necessary during each cycle of therapy and following its completion. Pro-active assessment of anticipated adverse events is essential including those that may occur late (following immunotherapy, for example). Telephone follow-up may be considered for some patients. A patient-focused approach is paramount throughout the pathway with expedient intervention of symptom management, multi-disciplinary approach including palliative care input, and community support. Related Documents Optimal Lung Cancer Pathway Version 4.0;Lung Cancer Clinical Expert Group, 2023 NICEGuidance: www.nice.org.uk/guidance/ng122 NICEQuality Standards: www.nice.org.uk/guidance/qs17 https://pathways.nice.org.uk/pathways/lung-cancer NICESACTalgorithms www.nice.org.uk/guidance/ng122/resources NHSLong Term Plan: www.england.nhs.uk/long-term-plan/ Commissioning Guidance for the Whole Lung Cancer Pathway CEG2024/25(in preparation)

11. Timed Treatment Pathway 3: Radiotherapy This pathway was developed by members of the CEG for Lung Cancer and Mesothelioma, NHSE and led by D Gilligan, M Hatton, and L Toy Maximum Times Best Practice Pointers National Optimal Lung Cancer Pathway Diagnostic Standards of Care • Continuous tracking and navigation • Electronic or structured referral document Multidisciplinary Team meeting Staging, Performance status, pathology including typing and molecular markers available • Day 21 (day 18 for SCLC) Fast track referral to clinical oncology for all lung cancer within 24 hours Non-small cell lung cancer Small cell lung cancer Limited stage • Pre-book radiotherapy treatment Day 28 (day 25 for SCLC) • Optimise comorbidities e.g. COPD, smoking, nutrition as early in the pathway as possible2. Oncology Clinic (within 3 working days latest day 33) Face to face optimal Oncology Clinic (within 3 working days latest day 25) Face to face optimal • LCNS - Support patient to make informed choices and give information/ clarity to complex treatments. Benefits/compensation/ community referrals First Day 35 (day 32 for SCLC) Chemotherapy (within 7 days) • Oncology clinic same day as MDT for assessment for radical/chemo radiotherapy Day 42 Radical: First Treatment preferably starts within 14 days for SABR or radical radiotherapy Palliative: First Treatment (within 14 days) • Joint clinical/medical oncology clinics for chemo-radiotherapy patients Day 49 • Joint surgical/ clinical oncologist appointment for all operable stage 3 patients and for patients with earlier stage and borderline fitness for surgery. Chemo-radiotherapy: Treatment start within 21 days with Radiotherapy given with first cycle or second cycle • Single-visit whenever possible. Day 60 Radiotherapy to start with second cycle • Post treatment assessment of suitability for immunotherapy / surgery. Trial screening • Peer review of all radical radiotherapy plans • Avoid treatment interruptions in radical RT

12. Appendix 1: Diagnostic Standards of Care for suspected lung cancer

13. Peripheral lesion with normal hilar and mediastinal appearances on staging CT with no distant metastases DSOC 1: Assess contrast-enhanced CT of lower neck, thorax and upper abdomen Broadly assess for fitness for treatment Proceed with this standard of care where patients are thought to be fit enough for, and willing to undergo, investigations and treatment. Patients who are unfit for, or unwilling investigations and treatment, should be discussed at the MDT meeting to explore further options including care. to undergo supportive ‘Peripheral lesion’ = positioned in the outer 2/3 of the thorax based on axial CT image (blue area); not involving central structures (red area) Notes and guidance Percutaneous image-guided biopsy is the preferred method of suspected primary tumour biopsy after PET where possible given the higher sensitivity. Bronchoscopic guided biopsy is consideredwhere percutaneousis high risk and /or where CT shows a bronchus leading directly into the tumour (bronchus sign). This DSOC includes solid pulmonary nodules ≥8mm diameter / ≥300mm3volume with a Brock risk of malignancy ≥10% or persistent sub-solid nodules for ≥3 months with a solid component ≥5mm. Smaller nodules are excluded from this DSOC. Pure ground glass nodules usually do not require further diagnostics and should continue under surveillance. Further invasive investigations or intervention may be indicated if a solid component develops. A specialist supportive/palliative care review can be considered for patients for whom the MDT treatment decision is ‘best supportive care’ and/or with uncontrolled symptoms. Commence prehabilitation / optimisation at first assessment – Ensure the pillars of prehabilitation are covered: Offer smoking cessation Encourage physical activity Prevent and manage malnutrition Refer to Lung Cancer Nurse Specialist Consider participation in research Physiology tests (request simultaneously) Physiology tests (request simultaneously) Diagnostic and staging tests Request Diagnostic and Staging Bundle: Request Fitness assessment: • Spirometry and transfer factor • Consider one or more of: Shuttle walk*, or CPEX* • ECG • Consider perfusion scan if pneumonectomy Request echocardiogram if*: • Heart murmur • Abnormal ECG • Known ischaemic heart disease / valvular disease • Possibility of pneumonectomy Assessment by a cardiologist may be required *May be omitted if surgery not an option Request Fitness assessment: • PET-CT (complete within 5 days); pre-book primary tumour biopsy. Review PET-CT avoiding full MDT discussion and if clear of nodal or distant metastases, proceed with biopsy. Where PET-CT upstages the tumour, to: N1-3 M0 see DSOC 2; N0-3 M1 see DSOC 4 • Percutaneous image-guided biopsy OR bronchoscopic guided biopsy (Fluoroscopy, radial EBUS, navigational bronchoscopy) • Some MDTs may consider it appropriate to offer treatment without a biopsy if there is no upstaging on PET and the probability of malignancy is sufficiently high • Contrast-enhanced CT brain for suspected stage II (T >4cm) • Consider alerting surgical or radiotherapy service early. Dataset for MDT discussion: PET-CTresults Diagnostic and staging test; usually percutaneous lung biopsy if done; may be other. Performance status, FEV1 and DLCO Additionalfitness tests as necessary Lung Cancer Diagnostic Standard of Care Bundle 1 (DSOC 1)

14. Lesion with mediastinal / hilar lymphadenopathy without distant metastases on staging CT DSOC 2: Assess contrast-enhanced CT of lower neck, thorax and upper abdomen Broadly assess for fitness for treatment Proceed with this standard of care where patients are thought to be fit enough for, and willing to undergo, investigations and treatment. Patients who are unfit for, or unwilling to undergo investigations and treatment, should be discussed at the MDT meeting to explore further options including supportivecare. Notes and guidance Staging EBUS ± EUS should be performed where there are enlarged nodes, including isolated N1 hilar nodes and where there is FDG avidity in normal sized nodes. PET-CT has a significant false negative rate, so sampling of normal sized, PET negative nodes is recommended when nodal appearances are not typically benign on CT or endosonography. Where staging EBUS ± EUS is performed there should be a systematic examination of mediastinal and hilar lymph nodes beginning with N3 stations, followed by N2 and finally N1. Any accessible lymph node based on CT (≥10mm), PET-CT (FDG avidity above the mediastinalblood pool)or sonographicassessment,is sampled. A specialist supportive/palliative care review should be routinely offered to all patients for whom the MDT treatmentdecisionis ‘best supportive care’ and/or uncontrolledsymptoms. Commence prehabilitation / optimisation at first assessment – Ensure the pillars of prehabilitation are covered: Offer smoking cessation Encourage physical activity Prevent and manage malnutrition Refer to Lung Cancer Nurse Specialist Consider participation in research Physiology tests (request simultaneously) Diagnostic and staging tests Request Fitness assessment: Request Diagnostic and Staging Bundle: • Spirometry and transfer factor • Consider one or more of: Shuttle walk*, or CPEX* • ECG • Consider perfusion scan if pneumonectomy • PET-CT (complete within 5 days); pre-book staging EBUS ± EUS . Review PET-CT avoiding full MDT discussionand proceed as below. Where PET-CT upstages the tumourto M1 see DSOC 4 • Proceed with staging EBUS ± EUS where no SCN seen. • US guided nodal biopsy where CT or PET-CT show enlarged or FDG avid supraclavicular nodes (SCN) • Biopsy of the primary lesion where nodes negative on EBUS ± EUS • Reflex predictive biomarker testing is preferred • Contrast-enhanced CT brain for suspected stage II (or if known small cell). • Contrast-enhanced MR brain for suspected stage III Request echocardiogram if*: • Heart murmur • Abnormal ECG • Known ischaemic heart disease / valvular disease • Possibility of pneumonectomy Assessment by a cardiologist may be required *May be omitted if surgery not an option Dataset for MDT discussion: PET-CT and CT or MR brainresults Bronchoscopy / EBUS ± EUS/ other pathology Performance status, FEV1and DLCO Additional fitness tests as required Lung Cancer Diagnostic Standard of Care Bundle 2 (DSOC 2)

15. Contiguous or conglomerate invasive mediastinal lymphadenopathy without distant metastases on staging CT DSOC 3: Assess contrast-enhanced CT of lower neck, thorax and upper abdomen Broadly assess for fitness for treatment Proceed with this standard of care where patients are thought to be fit enough for, and willing to undergo, investigations and treatment. Patients who are unfit for, or unwilling to undergo investigations and treatment, should be discussed at the MDT meeting to explore further options includingsupportive care. Notes and guidance This category of patients may be suitable for treatment with curative intent using radiotherapy or chemoradiotherapy. Mediastinal nodes contiguous with the primary tumour or conglomerate are almost always involved and sampling may proceed to confirm diagnosis. There is a high chance of metastatic disease. Diagnostic EBUS refers to the targeted sampling of nodal disease for pathological confirmation, tumour sub- typing and molecular pathology. “Invasive mediastinal lymphadenopathy” has poorly defined borders and cannot be easily measured. It forms conglomerate disease with other nodal stations. A specialist supportive/palliative care review should be routinely offered to all patients for whom the MDT treatment decision is ‘best supportive care’ and/or uncontrolled symptoms. Commence prehabilitation / optimisation at first assessment – Ensure the pillars of prehabilitation are covered: Offer smoking cessation Encourage physical activity Prevent and manage malnutrition Refer to Lung Cancer Nurse Specialist Consider participation in research Diagnostic and staging tests Physiology tests (request simultaneously) Request Fitness assessment: Request Diagnostic and Staging Bundle: • Spirometry and transfer factor† • Renal function • PET-CT (complete within 5 days); pre-book Bronchoscopy/ EBUS ± EUS / SCN node biopsy. Review PET-CT; where no upstaging patient is potentially appropriate for curative treatment. Where PET-CT upstages the tumour:to N0-3 M1 see DSOC 4 • Proceed with EBUS ± EUS or where no SCN or US negative (staging EBUS may be required to define tumour extent) • US guided nodal biopsy where CT or PET-CT show enlarged or FDG avid supraclavicular nodes (SCN) † transfer factor may be omitted if does not influence treatment • Contrast-enhanced MR brain. (CT if known small cell) • Reflex predictive biomarker testing is preferred Dataset for MDT discussion: PET-CT and MR brainresults Bronchoscopic/ EBUS / other pathology Performance status, FEV1and DLCO Renal function Lung Cancer Diagnostic Standard of Care Bundle 3 (DSOC 3)

16. DSOC 4: Distant metastases on staging CT Assess contrast-enhanced CT of lower neck, thorax and upper abdomen Broadly assess for fitness for treatment Proceed with this standard of care where patients are thought to be fit enough for, and willing to undergo, investigations and treatment. Patients who are unfit for, or unwilling to undergo investigations and treatment, should be discussed at the MDT meeting to explore furtheroptions including supportive care. Notes and guidance Follow this algorithm in cases where there is clear evidence of distant metastases on CT. Sometimes this may need to be clarified with additional tests e.g. liver US/MR/CT or PET-CT. A specialist Supportive/Palliative care review should be routinely offered to all patients, irrespective of any other treatment offered and/or uncontrolled symptoms. Diagnostic EBUS refers to the targeted sampling of nodal disease for pathological confirmation. It is essential that pathological samples are adequate to guide targeted treatment. Staging EBUS may be required to clarify tumour volume. Synchronous brain metastases may be suitable for stereotactic radiosurgery or surgery and should be discussed at the brain metastases MDT. See separate notes for metachronous oligometastatic disease. Commence prehabilitation / optimisation at first assessment – Ensure the pillars of prehabilitation are covered: Offer smoking cessation Encourage physical activity Prevent and manage malnutrition Refer to Lung Cancer Nurse Specialist Consider participation in research Physiology tests (request simultaneously) Diagnostic and staging tests Request Diagnostic and Staging Bundle: Request Fitness assessment: • Spirometry optional • Renal function Choose the least invasive and safest sampling technique to yield adequate pathology for tumour sub-typing and targeted therapy assessment. Options include: • Diagnostic bronchoscopy (±TBNA) • Diagnostic EBUS • US or CT guided biopsy of any target area • Pleural aspiration ± medical thoracoscopy if pleural effusion. • Predictive biomarker result within 10 working days (facilitated by reflex testing) • Bone biopsy should be avoided where there is no significant soft tissue component because of decalcification time and inability to do molecular pathology • Consider PET-CT and contrast enhanced CT brain for oligometastatic disease (see separate notes) Dataset for MDT discussion: Bronchoscopic/ EBUS / other pathology Performance status, Renal function Lung Cancer Diagnostic Standard of Care Bundle 4 (DSOC 4)

17. Notes for all Lung Cancer SOCs EBUS ± EUS: The majority of assessments will involve EBUS only but EUS or EUSB may be added where indicated. Staging EBUS ± EUS: Patients may need to be referred to a specialist centre for this. There should be a mechanism for rapid e-referral and prompt testing in line with the National OptimalLung Cancer Pathwayand the NHSE EBUS service specification. Reflex testing: refers to the block testing of pathological samples to assess for suitability for targeted therapy. The specific tests depend on the drugs available so will change as new drugs are approved for use. Oligometastatic Disease Synchronous brain metastases may be treated by surgery or stereotactic radiosurgery. MDTs may also elect to treat other synchronous oligometastatic sites by surgery on an individual basis (no current guidance). NHS England have published eligibility criteria for consideration of SABR for oligometastatic disease (see link below) in summary: • Confirmed histologicaldiagnosis • 1-3 sites of metastatic disease confined to 1 – 2 extracranial organs which can be treated with SABR to a radical radiation dose. • Maximumsize of any single metastasis5cm • Diseasefree interval from primary treatment> 6 months • Life expectancy> 6 months • WHO performance status≤ 2 • All patients to be discussed at SABR MDT with presence of, or prior discussion with a disease site specific oncologist Abbreviations CT: computed tomography PET-CT: Positron emission tomography and computed tomography US: Ultrasound MRI: Magnetic resonance imaging EBUS: Endobronchial ultrasound with needle sampling. Here refers to linear EBUS unless radial US specified EUS / EUSB: Endoscopic ultrasound / Endoscopic ultrasound with EBUS scope CPEX: Cardiopulmonary exercise test ECG: Electrocardiogram SABR: Stereotactic Ablative Body Radiation MDT: Multidisciplinary Team Oligometastatic guidelines: www.england.nhs.uk/wp-content/uploads/2020/03/1908-cc-policy- sbar-for-metachronous-extracranial-oligometastatic-cancer.pdf